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D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness

Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland

Requests for reprints: Baolin Zhang, Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, Building 29A, Room 2B-24, Bethesda, MD 20892. Phone: 301-827-1784; Fax: 301-480-3256; E-mail: Baolin.zhang{at}fda.hhs.gov.

D4-GDI is a Rho GDP dissociation inhibitor that is widely expressed in hematopoietic cells. Its possible expression and function in breast cancer cells has not been described. Here, we found that D4-GDI is expressed in a panel of breast cancer cell lines, but not in benign-derived mammary epithelial cells. Knockdown of D4-GDI expression in MDA-MB-231 cells by RNA interference blocks cell motility and invasion. The cells lacking D4-GDI grown on Matrigel revert to a normal breast epithelial phenotype characterized by the formation of cavitary structures. Silencing D4-GDI expression inhibits ß1-integrin expression and cell-matrix adhesion. Reintroduction of D4-GDI fully restored both ß1-integrin expression and cellular invasion. Knockdown of D4-GDI in BT549 cells results in a similar effect. These results show that D4-GDI modulates breast cancer cell invasive activities. (Cancer Res 2006; 66(11): 5592-8)

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